The size of a fish is an important factor in its physiology, and metal uptake is affected by animal physiology. In this study, small and large tilapias (Oreochromis niloticus) differing approximately twofold in length and fivefold in weight were compared for their antioxidant response. Both groups were exposed to Cu or Cr (1.0 mu g/mL) in a freshwater (-80 mg CaCO3/L, conductivity 1.77 mS/cm) using 2 exposure protocols (20 mu M for 48 h and 10 mu M for 6 days). Following the exposures, the antioxidant enzyme activities (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX; glutathione reductase, GR and glutathione S-transferase, GST) and glutathione (GSH) levels were measured in the liver of fish. Results showed that small fish was affected from exposure conditions much more than large ones as their antioxidant parameters significantly decreased even in controls. Metal exposures of small fish caused significant increases in SOD and CAT activity in acute Cu or Cr exposures. Subchronic Cr exposure of small fish also caused significant increases in CAT, GPx and GST activities, while there was no significant change in Cu-exposed ones. Large fish, however, showed different antioxidant responses as their levels mostly decreased. This study demonstrated that the response of antioxidant system in the liver of tilapia varied in relation to fish sizes and emphasized using different size groups in environmental monitoring and also in evaluation of fish biomarkers.